Bora Bidisha, Das Namisha, Sultana Jakia Parbin, Raza Md Kausar, Goswami Tridib K
Department of Chemistry, Gauhati University, Guwahati 781014, Assam, India.
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India.
Dalton Trans. 2025 Jul 29;54(30):11743-11756. doi: 10.1039/d4dt03432e.
Herein, we synthesized, characterized and explored the photo-triggered anticancer activity of five Mn(III) porphyrins Mn1-Mn5, (diaqua)-(tetraphenylporphyrinato)manganese(III) propionate, Mn(III)TPP(HO) or Mn1; (diaqua)-tetrakis(4-methylphenylporphyrinato)manganese(III) propionate, Mn(III)TMeP(HO) or Mn2; (diaqua)-tetrakis(4-methoxyphenylporphyrinato)manganese(III) propionate, Mn(III)TMP(HO) or Mn3; (diaqua)-tetrakis(4-fluorophenylporphyrinato)manganese(III) propionate, Mn(III)FTPP(HO) or Mn4 and (diaqua)-tetrakis(4-chlorophenylporphyrinato)manganese(III) propionate, Mn(III)ClTPP(HO) or Mn5, which remain virtually unexplored as photodynamic therapy (PDT) agents like other paramagnetic metalloporphyrins. These Mn(III) porphyrins, bearing different -substituents on their -phenyl rings and two water molecules as axial ligands, were characterized using spectroscopic techniques and structurally through single-crystal X-ray diffraction, revealing an octahedral MnNO geometry. Binding studies demonstrated a strong affinity of the metalloporphyrins for human serum albumin (HSA), indicating their potential for biological applications. The visible light-assisted generation of reactive oxygen species (ROS) by these Mn(III) porphyrins was confirmed 1,3-diphenylisobenzofuran (DPBF) titration, identifying singlet oxygen (O) as one of the primary ROS. Photoredox activity under visible light, displayed by the Mn(III) porphyrins in the presence of ascorbic acid involving +3 and +2 oxidation states of manganese, further underscores the photochemotherapeutic potential of Mn1-Mn5. The ROS generation ability was further validated intracellularly in HeLa cells using Mn4 with the help of 2',7'-dichlorofluorescein diacetate (DCFDA) assay under visible light irradiation ( = 400-700 nm). Furthermore, among the five Mn(III) porphyrin complexes (Mn1-Mn5) evaluated for photo-triggered anticancer activity using MTT assays, Mn4 exhibited superior photocytotoxicity, with a half-maximal inhibitory concentration (IC) of 4.93 ± 0.7 μM against HeLa cancer cells under visible light irradiation and negligible dark toxicity (IC > 50 μM). These results suggest that both type-I and type-II ROS generation pathways contribute to the observed photocytotoxicity. This study highlights the potential of paramagnetic metalloporphyrins, particularly Mn(III) porphyrins, in anticancer application by demonstrating their effectiveness as photosensitizers for photodynamic cancer therapy.
在此，我们合成、表征并探究了五种锰（III）卟啉Mn1 - Mn5的光触发抗癌活性，即丙酸（二水） - （四苯基卟啉合）锰（III），Mn(III)TPP(HO) 或Mn1；丙酸（二水） - 四（4 - 甲基苯基卟啉合）锰（III），Mn(III)TMeP(HO) 或Mn2；丙酸（二水） - 四（4 - 甲氧基苯基卟啉合）锰（III），Mn(III)TMP(HO) 或Mn3；丙酸（二水） - 四（4 - 氟苯基卟啉合）锰（III），Mn(III)FTPP(HO) 或Mn4以及丙酸（二水） - 四（4 - 氯苯基卟啉合）锰（III），Mn(III)ClTPP(HO) 或Mn5，与其他顺磁性金属卟啉一样，它们作为光动力疗法（PDT）药物几乎未被探索。这些锰（III）卟啉在其苯基环上带有不同的取代基且有两个水分子作为轴向配体，通过光谱技术进行了表征，并通过单晶X射线衍射确定了结构，揭示出八面体MnNO几何构型。结合研究表明金属卟啉对人血清白蛋白（HSA）具有很强的亲和力，表明它们在生物应用方面具有潜力。通过1,3 - 二苯基异苯并呋喃（DPBF）滴定证实了这些锰（III）卟啉在可见光辅助下产生活性氧（ROS），确定单线态氧（O）是主要的ROS之一。锰（III）卟啉在抗坏血酸存在下在可见光下表现出的光氧化还原活性，涉及锰的 +3和 +2氧化态，进一步强调了Mn1 - Mn5的光化学治疗潜力。在可见光照射（ = 400 - 700 nm）下，借助2',7' - 二氯荧光素二乙酸酯（DCFDA）测定法，使用Mn4在HeLa细胞内进一步验证了ROS生成能力。此外，在使用MTT测定法评估光触发抗癌活性的五种锰（III）卟啉配合物（Mn1 - Mn5）中，Mn4表现出卓越的光细胞毒性，在可见光照射下对HeLa癌细胞的半最大抑制浓度（IC）为4.93 ± 0.7 μM，且暗毒性可忽略不计（IC > 50 μM）。这些结果表明I型和II型ROS生成途径都对观察到的光细胞毒性有贡献。本研究通过证明顺磁性金属卟啉，特别是锰（III）卟啉作为光动力癌症治疗的光敏剂的有效性，突出了其在抗癌应用中的潜力。
